Cysteine conjugates of acetaminophen and p-aminophenol are potent inducers of cellular impairment in human proximal tubular kidney HK-2 cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020751" target="_blank" >RIV/62690094:18470/23:50020751 - isvavai.cz</a>
Alternative codes found
RIV/00216275:25310/23:39920318
Result on the web
<a href="https://link.springer.com/article/10.1007/s00204-023-03569-2" target="_blank" >https://link.springer.com/article/10.1007/s00204-023-03569-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00204-023-03569-2" target="_blank" >10.1007/s00204-023-03569-2</a>
Alternative languages
Result language
angličtina
Original language name
Cysteine conjugates of acetaminophen and p-aminophenol are potent inducers of cellular impairment in human proximal tubular kidney HK-2 cells
Original language description
Acetaminophen (APAP) belong among the most used analgesics and antipyretics. It is structurally derived from p-aminophenol (PAP), a potent inducer of kidney toxicity. Both compounds can be metabolized to oxidation products and conjugated with glutathione. The glutathione-conjugates can be cleaved to provide cysteine conjugates considered as generally nontoxic. The aim of the present report was to synthesize and to purify both APAP- and PAP-cysteine conjugates and, as the first study at all, to evaluate their biological effects in human kidney HK- 2 cells in comparison to parent compounds. HK-2 cells were treated with tested compounds (0-1000 mu M) for up to 24 h. Cell viability, glutathione levels, ROS production and mitochondrial function were determined. After 24 h, we found that both APAP- and PAP-cysteine conjugates (1 mM) were capable to induce harmful cellular damage observed as a decrease of glutathione levels to 10% and 0%, respectively, compared to control cells. In addition, we detected the disappearance of mitochondrial membrane potential in these cells. In the case of PAP-cysteine, the extent of cellular impairment was comparable to that induced by PAP at similar doses. On the other hand, 1 mM APAP-cysteine induced even larger damage of HK-2 cells compared to 1 mM APAP after 6 or 24 h. We conclude that cysteine conjugates with aminophenol are potent inducers of oxidative stress causing significant injury in kidney cells. Thus, the harmful effects cysteine-aminophenolic conjugates ought to be considered in the description of APAP or PAP toxicity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
<a href="/en/project/GA19-11867S" target="_blank" >GA19-11867S: Research on toxicity mechanism of S-conjugates of aminophenolic drugs</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of toxicology
ISSN
0340-5761
e-ISSN
1432-0738
Volume of the periodical
97
Issue of the periodical within the volume
11
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
2943-2954
UT code for WoS article
001069599300001
EID of the result in the Scopus database
2-s2.0-85168920205